Gastrointestinal diseases caused by rotaviruses and related agents constitute serious health problems for children living in the United States and other areas of the world. Breast feeding has been identified as a major factor in decreasing the morbidity and mortality associated with acute diarrheal disease; however the mechanisms associated with this protection have not been fully elucidated. We have identified a macromolecular component of the human milk fat globule which inhibits the replication of a wide range of rotavirus strains. The anti-viral activity is associated with acidic glycoprotein fractions which do not contain immunoglobulins. Reactivity with monoclonal antibodies indicates that the active material is a component of the milk mucin complex and that it exerts its activity by binding to virions. Studies with an animal model system document that the oral administration of the milk-derived glycoprotein can prevent the development of rotavirus gastroenteritis. We propose a series of experiments to purify and characterize the anti-viral component of human milk. We will determine the oligosaccharide linkages which are essential for anti-viral activity. We will also define the viral epitopes which are the targets of the mucin binding. we propose to generate large amounts of the milk-derived anti-viral factor and determine the stability of the active material under a range of environmental conditions. These studies may result in the identification of a novel anti-viral factor in human milk and in the subsequent development of a new therapeutic modality for the prevention and treatment of viral gastroenteritis.